Effects of Moderate Hyperbilirubinemia on Nutritive Swallowing and Swallowing-Breathing Coordination in Preterm Lambs

Abstract

Background: Hyperbilirubinemia (HB) occurs in 90% of preterm newborns. HB induces acute neurological disorders (somnolence, abnormal tone, feeding difficulties, auditory dysfunction) and alterations in respiratory control. These findings suggest brainstem neurotoxicity that could also affect swallowing centers. Objective: To test the hypothesis that HB impairs nutritive swallowing (NS) and swallowing-breathing coordination. Methods: Two groups of preterm lambs (born 14 days prior to term), namely control (n = 6) and HB (n = 5), were studied. On day 5 of life (D0), moderate HB (150-250 µmol/l) was induced during 17 h in the HB group. Swallowing was assessed via recording of pharyngeal pressure and respiration by respiratory inductance plethysmography and pulse oximetry. The effect of HB on NS was assessed during standardized bottle-feeding. A second recording was performed 48 h after recovery from HB (D3). Results: Swallows were less frequent (p = 0.003) and of smaller volume (p = 0.01) in HB lambs while swallowing frequency was decreased (p = 0.004). These differences disappeared after HB normalization. Swallowing-breathing coordination was impaired in HB lambs, with a decrease in percent time with NS burst-related apneas/hypopneas at D0 and D3. Simultaneously, HB lambs tended to experience more severe desaturations (<80%) during bottle-feeding. Finally, following bottle-feeding, the respiratory rate was significantly lower, along with an increased apnea duration in HB lambs. Conclusions: Swallowing and swallowing-breathing coordination are altered by acute moderate HB in preterm lambs. Decreased efficiency at bottle-feeding is accompanied by continuation of breathing during swallow bursts, which may promote lung aspiration.

Moderate Hyperbilirubinemia Alters Neonatal Cardiorespiratory Control and Induces Inflammation in the Nucleus Tractus Solitarius

“…Sixteen preterm lambs were born vaginally on gestational day 133 (term = 147 days) as previously described (Boudaa et al, 2013 ). Results on the effects of HB on bottle-feeding efficiency and nutritive swallowing-breathing coordination obtained in the same preterm lambs have previously been published (Bourgoin-Heck et al, 2015 ). Premature labor was induced by mifepristone (8 mg/kg), preceded by betamethasone (12 mg × 2).…”

“…Furthermore, a study in rat pups provided evidence that acute HB influences respiratory control; however, the degree of HB was much higher and more transient than levels clinically encountered in neonates (Mesner et al, 2008 ). More recently, we showed a decreased efficiency in bottle-feeding and an impaired swallowing-breathing coordination in a novel experimental model of sustained and moderate HB in preterm lambs (Bourgoin-Heck et al, 2015 ). Overall, the above studies suggest that HB induces respiratory alterations in the neonate.…”

“…Premature labor was induced by mifepristone (8 mg/kg), preceded by betamethasone (12 mg × 2). A unique preterm lamb model for moderate HB was designed for the purposes of the study (Bourgoin-Heck et al, 2015 ). Briefly at birth, lambs were randomly assigned to either the HB group or control group.…”

“…Briefly at birth, lambs were randomly assigned to either the HB group or control group. On postnatal day 5, HB was induced by an intravenous infusion of 20 mg/kg of the bilirubin solution, stabilized with albumin and diluted in Ringer's Lactate buffer (Hansen et al, 1992 ; Mesner et al, 2008 ; Bourgoin-Heck et al, 2015 ), whereas control lambs received a bilirubin-free solution. Bilirubinemia was maintained between 150 and 250 μmol/L for a period of 17 h.…”

Hyperbilirubinemia Influences Sleep-Wake Cycles of Term Newborns in a Non-Linear Manner

“…Since the syndrome contained in BIND is generally related to cognitive functions, damage to neural plasticity may be one of the pathogenesis of BIND. In addition, the brain damage caused by bilirubin can be expressed as an increase of central apnea [19] or swallowing dysfunction [20]. These changes are also caused by the less severe jaundice.…”